Bone implant and systems that controllably releases silver

ABSTRACT

Silver and/or zinc ion releasing implants, systems and method of operating, inserting and activating/inactivating them are described. In some variations the implant is configured as a bone implant that includes a bone-screw or intramedullary rod like body configured to receive a treatment cartridge having a plurality of ion-releasing members configured as an anode that can controllably engage with a catheter to turn galvanic release of ions on/off as desired. These devices may be configured to release silver ions (and/or zinc ions) above a predetermined level for a predetermined period of time and may maintain a concentration of ions over a relatively large volume of tissue. The ion-releasing members may be configured to reduce or prevent implant movement.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.13/748,546, filed on Jan. 23, 2013, titled BONE IMPLANT AND SYSTEMS THATCONTROLLABLY RELEASES SILVER,” Publication No. US-2013-0144204-A1, whichis a divisional of U.S. patent application Ser. No. 13/231,219, filed onSep. 13, 2011, titled “BONE IMPLANT AND SYSTEMS THAT CONTROLLABLYRELEASES SILVER,” now U.S. Pat. No. 8,771,323, which claims priority tothe following U.S. provisional patent applications: U.S. ProvisionalPatent Application No. 61/413,230, filed on Nov. 12, 2010, and titled“SILVER ELUTING BONE IMPLANTS AND METHODS OF USE”; U.S. ProvisionalPatent Application No. 61/438,162, filed on Jan. 31, 2011, and titled“BONE SUPPORTING IMPLANTS WITH ANTIBACTERIAL PROPERTIES”; U.S.Provisional Patent Application No. 61/447,393, filed on Feb. 28, 2011,and titled “INTRAMEDULLARY (INTRAOSSEAL) ROD, NAIL OR CATHETER WITHGALVANICALLY PRODUCED ANTIBACTERIAL PROPERTIES”; U.S. Provisional PatentApplication No. 61/465,350, filed on Mar. 18, 2011, and titled“ANTIMICROBIAL IMPLANT TO PROVIDE MECHANICAL SUPPORT FOR A BORE THATUTILIZES A GALVANIC POTENTIAL BETWEEN TWO OR MORE METALS TO CREATE IONSTHAT ARE GERMICIDAL AND/OR ANTIFUNGAL”; U.S. Provisional PatentApplication No. 61/516,388, filed on Apr. 4, 2011, and titled “GALVANICANTIMICROBIAL BONE SCREW FOR THE TREATMENT OF DISEASED, FRACTURE ORMISALIGNED BONE AND TO PROMOTE BONE GROWTH AND REGENERATION”, each ofwhich is incorporated by reference in its entirety.

INCORPORATION BY REFERENCE

All publications and patent applications mentioned in this specificationare herein incorporated by reference to the same extent as if eachindividual publication or patent application was specifically andindividually indicated to be incorporated by reference.

BACKGROUND

Osteomyelitis is an infection of a bone by a microorganism such asbacteria or fungi. Diabetes, joint replacement, trauma, and injecteddrug use can lead to osteomyelitis. As people live longer, incidences ofosteomyelitis are expected to increase. To complicate matters, aninfection, such as following joint replacement surgery, can occur longafter the incision has been closed. An infection buried in a bone can bedifficult to detect; it is not visible to the eye and taking a culturesample is difficult and painful. Once diagnosed, antibiotics caneliminate many infections. Unfortunately, microorganisms are developingresistances rendering existing antibiotics useless. Reports of patientsinfected with microorganisms resistant to regular and “last resort”antibiotics are increasing in number. For these patients, there are fewor no effective options. The problem is expected to become worse asmicroorganisms exchange genetic material and more species becomeresistant to antibiotics. Prophylactic use of antibiotics, althoughcommonly done, is discouraged because it may increase antibioticresistance. Infection with methicillin resistant Staphylococcus aureus(MRSA) is a significant health problem that is expected to worsen.Additionally, microorganisms on the surface of an artificial joint orother implanted device can cooperate to create an impervious layer,called a biofilm. A biofilm may form a mechanical barrier to anantibiotic.

Silver is known to be antimicrobial and has been used (primarily as acoating) in various medical devices with limited success. Both active(e.g., by application of electrical current) and passive (e.g.,galvanic) release of silver ions have been proposed for use in thetreatment and prevention of infection. However, the use ofsilver-releasing implants have been limited because of the difficulty incontrolling and distributing the release of silver ions as well as thedifficulty in maintaining a therapeutically relevant concentration ofsilver ions in an appropriate body region. Zinc shares many of the sameantimicrobial properties of silver, but have been less commonly used,and thus even less is known about how to control the amount anddistribution of the release of silver ions to treat and/or preventinfection.

Thus, it would be highly desirable to provide device systems and methodsfor the controlled release (particularly the controlled galvanicrelease) of a high level of silver, zinc or silver and zinc ions intothe tissue for a sufficient period of time to treat or preventinfection.

Specifically, known systems and devices that have attempted to use ions(e.g., silver and/or zinc) to treat infection have suffered fromproblems such as: insufficient amounts of ions released (e.g., ionconcentration was too low to be effective); insufficient time fortreatment (e.g., the levels of ions in the body or body region were notsustained for a long enough period of time); and insufficient region orvolume of tissue in which the ion concentration was elevated (e.g., thetherapeutic region was too small or limited, such as just on the surfaceof a device). Further, the use of galvanic release has generally beenavoided or limited because it may effectively corrode the metalsinvolved, and such corrosion is generally considered an undesirableprocess, particularly in a medical device.

In general, controlled release of silver and/or zinc ions would bebeneficial. Control of the release of ions may allow the treatment ofthe patient to be regulated by turning the release on/off. In general,silver coated devices do not typically allow for the controlled releaseof ions. Silver coatings or impregnations do not typically allowcontrolled release, because they are always “on” (e.g., always releasingsilver) to some degree. Zinc coatings on traditional implants may sufferfrom the same problem. Since release depends on the ionic concentrationof body fluids, the actual release (and therefore concentration) of ionsmay be difficult to predict and control.

Therapeutically, the level of silver and/or zinc ions released into abody is important, because it may determine how effective theantimicrobial ions are for treating or preventing infection. Asdescribed in greater detail below, the amount or ions releasedgalvanically may depend on a number of factors which have not previouslybeen well controlled. For example, galvanic release may be related tothe ratio of the anode to the cathode (and thus, the driving force) aswell as the level of oxygen available; given the galvanic reaction, thelevel of oxygen may be particularly important for at the cathode.Insufficient oxygen at the cathode may be rate-limiting for galvanicrelease.

For example, with respect to silver, it has been reported that aconcentration of 1 mg/liter of silver ions can kill common bacteria in asolution. Silver ions may be generated a galvanic system with silver asthe anode and platinum or other noble metal as the cathode. However oneof the challenges in designing a galvanic system for creation of silverion in the body that has not been adequately addressed is theappropriate ratios of the areas of the electrodes (e.g., anode tocathode areas) in order to create the germicidal level of free silverions. One challenge in designing a galvanic system is addressing theparasitic loss of current due to formation of silver chloride viareaction:

AgCl+e→Ag+Cl(−) Eo=0.222volts

We herein propose that it may be beneficial to have an area of thecathode under common biological condition that is at least larger than8% of the silver area to sustain the germicidal level of silver ions.For the purpose of this discussion, the following assumptions have beenmade: for a concentration of: [H+]=10̂(−7) moles/liter; [OH−]=10̂(−7)moles/liter; [O2]=5*10̂(−3) moles/liter in the capillary; [Cl−]=0.1moles/liter. The values of the following were also assumed (as constantsor reasonable approximations): Faraday's constant, F=96000coulombs/mole; diffusivity of oxygen=0.000234 cm2/sec; diffusivity ofAg+=10̂(−6) cm2/sec; diffusivity of Cl−=10̂(−6) cm2/sec; R, Gasconstant=8.314 J K⁻¹ mol⁻¹; T, temp. K; Mw of silver=108 grams/mol;germicidal concentration of silver=10̂(−5) mol/liter.

At equilibrium, for a galvanic cell it is acceptable to assume that thetwo electrodes are at the same potential. Using the Nernst equation, theequilibrium concentration of oxygen when the silver ion is at thegermicidal level may be calculated:

E=Eo−(RT/nF)ln [(Activity of products)/(activity of reactants)]

E=Eo−(0.0592/n)Log [(product)/(reactant)]

For the half cell reaction at the anode (silver electrode):Ag→Ag(+)+e(−). This reaction is written as a reduction reaction below:

Ag(+)+e(−)→Ag Eo=0.800 volt  eq. (1)

[Ag+]=1 mg/liter*(gr/1000 mg)*(1 mol/108 (Mw of Ag))=10̂(−5)Ag+mole/liter; E=0.800−(0.0592/1)log [1/(10̂(−5)]. Based on this, theresulting E=8.00−(0.0592*5)=0.504 volt.

For the cathode, the reactions are:

O₂+2H₂O+4e(−)→4OH(−) Eo=0.401 volt  eq. (2)

O₂₊₄H(+)+4e(−)→2H₂O Eo=1.229 volt  eq. (3)

In dilute aqueous solutions these two reactions are equivalent. Atequilibrium the potential for the two half-cell potentials must beequal:

E=0.401−(0.0592/4)log {[OH(−)]̂4/[O2]}

E(silver)=0.504=0.401−(0.0592/4)log {[10̂−7]̂4/[O2]}

Solving for [O₂], the result is: [O₂]=10̂(−21) atm. The result of thisanalysis is that, thermodynamically speaking, as long as theconcentration of oxygen is above 10̂(−21), the concentration of thesliver ion could remain at the presumed germicidal level.

However, a parasitic reaction to creation of silver ions is theformation of AgCl due to reaction of Cl− at the silver electrode. Thehalf-cell potential for this reaction is:

AgCl+e(−)→Ag+Cl(−)Eo=0.222

Solving the Nernst equation for this reaction with E=0.504, theconcentration of chloride [Cl−]=2×10̂(−5). The importance of thisreaction becomes apparent in evaluating the current needed to compensatefor the losses of current due to this reaction and the increased inratio of the area of the cathode to the anode.

The current density per until area requirements of the device can beestimated by combining Fick's and Faraday equations: the silver lossesdue to diffusion of silver from the device can be calculated using theFick's equation:

j=D[C(d)−C(c)]/d  Fick's equation

The current needed to create the silver ions (A/cm2): i=j*n*F, where, jis the mass flux, C(d) is the concentration of the silver at the deviceand C(c) is concentration of silver at the capillary bed (=0). D is thediffusion coefficient of silver (10̂(−6)) cm2/sec, d is the averagedistance of the device from the capillary bed (assumed to be =0.5 cm inthe bone), F is Faraday's constant (96000 col./mol), and n is the chargenumber.

The combination of the two equations for silver diffusion gives:

i(Ag)=D*·n·F(C(d))/d

Thus:

$\begin{matrix}{{i({Ag})} = {\left\{ {{10\bigwedge\left( {- 6} \right)} \star 1 \star \left( {10\bigwedge\left( {- 5} \right)} \right) \star (96000) \star {\left( {5 \star {10\bigwedge\left( {- 3} \right)}} \right)\text{/}0.5}} \right\} \star}} \\{\left( {1\mspace{20mu} {liter}\text{/}1000\mspace{14mu} {cm}^{3}} \right)} \\{= {2 \star {{10\bigwedge\left( {- 9} \right)}{Amp}\text{/}{cm}^{2}}}}\end{matrix}$

The current needed to create the silver ions at the desiredconcentration is approximately 2 nanoAmp/cm². Similarly, the currentdensity (A/cm2) required to reduce the chloride ions from biologicallevel (0.1 molar) to the desired level of 2*10̂(−5) molar could becalculated. For this equation the approximate values of the constantsare D=10̂(−6), d=0.1 cm. The change in the Chloride concentration itassumed to be (0.1−2*10̂(−5))=0.1. The current needed to feed theparasitic reaction can then be determined:

$\begin{matrix}{{i({cl})} = {\left\{ {\left( {10\bigwedge\left( {- 6} \right)} \right) \star (1) \star (96000) \star {(0.1)\text{/}(0.1)}} \right\} \star \left( {1{lit}\text{/}1000\mspace{20mu} {cm}^{3}} \right)}} \\{= {9.6 \star {10\bigwedge\left( {- 5} \right)}}} \\{= {96\; {microAmp}\text{/}{Cm}^{2}}}\end{matrix}$

The total anodic current needed is: i(Ag)+i (Cl)=i(anodic)=96microAmps/cm². On the cathode, the reaction limitation is the flux ofoxygen form the source to the surface of the electrode. The maxi(cathodic) current could be approximated to:

$\begin{matrix}\left. {{i\left( {O\; 2} \right)} = {\left\{ 0.000324 \right) \star (4) \star (96000) \star {\left( {5 \star {10\bigwedge\left( {- 3} \right)}} \right)\text{/}(0.5)}}} \right\} \\{\left( {1{{lit}/1000}\mspace{14mu} {cm}^{3}} \right)} \\{= {1.24 \star {{10\bigwedge\left( {- 3} \right)}{Amps}\text{/}{cm}^{2}}}}\end{matrix}$

Since the total cathodic current must be equal to total Anodic current:

i(cathodic)*Area of the cathode=i(anodic)*Area of Anode=>Area of theCathode/Area of the anode=(96*10̂(−6)/(1.24*10̂(−3))=0.077

This suggests that the area of the cathode must be at least equal to 8%of that of anode.

In addition to the ratio of the cathode to the ratio of the anode,another factor affecting the release of silver ions that has notpreviously been accounted for in galvanic release of silver to treatinfection is the concentration of oxygen needed.

The concentration of the oxygen needed to power the galvanic system istypically higher than that of the equilibrium concentration, since thesystem must overcome the activation energy of the reactions(over-potential) and supply the additional current. In the model belowwe evaluated the concentration of the oxygen needed to overcome theactivation energy for the reactions. Using the Tafel equation:

η=β log [i/io]

where i=current density, n=the over-potential, 13=overpotential voltageconstant, and io=intrinsic current density. For platinum, the oxygenover-potential constants are: β=0.05 volt and io=10̂(−9) A/m². Usingi=9.6*10̂(−5) Amp then:

η=0.05 log [9.6*10̂(−5)/(10̂(−9))]

η=0.25 volt

Adding the over potential to the potential at the equilibrium (0.501volts), and the total working half-potential needed at the cathodebecomes equal to (0.501+0.25)=0.751.

Using the Nernst equation to determine the concentration of oxygen atthe cathode:

E=0.751=0.401−(0.0592/4)log {[OH(−)]̂4/[O2]}

Thus, the concentration of oxygen at the electrode should be at least7*10̂(−5) mole.

The results of this analysis show that an implanted galvanic systemwould benefit from having an area of the cathode to the area of theanode (A_(cathode)/A_(anode)) of greater that about 8% and theconcentration of the oxygen at the site of implant to be at least7*10̂(−5) moles per liter, which may avoid rate-limiting effect.

Thus, to address the problems and deficiencies in the prior artmentioned above, described herein are systems, methods and devices forprophylactically treating a patient to prevent an infection and optionsfor eliminating an existing infection, including those untreatable byany existing treatments. Described below are implants and methods forpreventing and treating bone infections using an implantable,controllable, and rechargeable bone screws.

SUMMARY OF THE DISCLOSURE

The systems, devices and methods described herein may generally be usedto treat or prevent infection, including bone infections such asosteomyelitis by the controlled release of silver, zinc, or silver andzinc ions. In particular, the systems, methods and devices describedherein may be configured to allow controllable galvanic release of ions(e.g., silver, zinc or silver and zinc ions) to treat or preventinfection. Many of the variations described herein may be used inconjunction with one or more implants that also structurally ortherapeutically support the patient, including particularly thepatient's bones.

In general, any of the implants described herein may be used to treatbone and/or soft tissue. In some variations the implants are boneimplants specifically, and may be configured to support as well as treatthe bone. For example, the implant may be used to secure (as a screw,nail, bolt, clamp, etc.) another member such as a plate, rod, or thelike, or the implant may itself include a support member such as a rod,plate, etc. In some variations, the implant is a soft tissue implantthat is configured to be secured within non-bone body structures.

Although many of the examples described herein are illustrateddescribing the release of silver ions, any of the devices, methods andsystems described may be configured for the release of zinc ions insteadof, or in addition to, silver ions. It may be beneficial to release bothzinc and silver ions. In some situations it may be beneficial to releasezinc rather than silver, or vice versa. For example, variations of thedevices releasing zinc may be used preferentially when the infectiontargeted is resistant to silver. Zinc may also “corrode” faster, e.g.,releasing ions more quickly and/or at a higher concentration thansilver, which may be avoided or exploited depending upon the context.

Described herein are systems, devices and methods for the controlledrelease of silver, zinc, or silver and zinc ions to treat or preventinfection that may address many of the problems identified above. Forexample, described herein are devices configured for the galvanicrelease of ions that may be controlled with an on/off switch mechanism.For example, in some variations the galvanic relationship can beregulated remotely (before or after the silver and/or zinc releasingimplant has been inserted into the body). In some variations the systemsand device may be configured so that the implant includes a separable orseparate cathode and/or anode. The anode region (e.g., silver, zinc, orsilver and zinc anode) may be placed central to the treatment regionwhile the cathode could be positioned in an oxygen-rich region that maybe separate from the treatment region (e.g., oxygenated blood). This mayallow effective treatment of even relatively anoxic regions, includingbone.

The devices and systems described herein may also be configured toregulate the effective cathode active surface area and anode activesurface area (e.g., making the cathode surface area much larger than theeffective anode surface area). For example, the cathode active surfacearea may be 5% greater (e.g., Au/Palladium), 8% (e.g., Au/Pt), 10%(e.g., Au/Ag), etc. than the anode surface area.

For example described herein are implants, including bone implants, forproviding antimicrobial treatment to a region of a bone (and/orsurrounding tissues) In some variations the implant includes: anelongate cannulated body having a threaded outer region; at least oneexit channel extending from the cannulated body and out through thethreaded outer region; and one or more silver, zinc, or silver and zincrelease members configured to extend from the cannulated body and out ofthe exit channel.

The ion release members may be configured as part of a removabletreatment cartridge that is configured to fit within the cannulated bodyof the implant so that the one or more ion release members extend fromthe cannulated body. Note, as used herein the phrase “treat” and“treatment” may include acute and prophylactic treatments.

In the simplest variation, the implant is configured as a bone screwthat is hollow or contains a hollow inner body region into which areplaceable/rechargeable treatment cartridge may be inserted and/orremoved. The cartridge may be itself screwed into the body, or it may beotherwise secured within the body. The cartridge may include one or more(e.g., a plurality) of ion release members extending or extendable fromthe cartridge and therefore the implant. An ion release member may beconfigured to release silver, zinc or silver and zinc. In general an ionrelease member may be configured as an elongate member such as an arm,wire, branch, or the like. The ion release member may be a wire (e.g.,silver wire), or it may be a coated member such as a Nitinol or othershape-memory member, including a silver and/or zinc coating. Asmentioned, the implant (or the treatment cartridge portion) may includea plurality of ion release members.

An implant may have one or more exit channels. In general the exitchannels may be openings from the inner hollow region (e.g. cannulatedbody) of the implant through a side wall of the implant and out,possibly in the threaded region. Thus, in some variations the exitchannel is configured to deflect the one or more ion release membersaway from a long axis of the implant. For example, the exit channel maybe configured to deflect the one or more ion release members against athread of the outer threaded region so that it deflects away from theimplant. In some variations a plurality of exit channels extendingthrough the cannulated body.

An implant may also include a guide (or guide element, including a rail,keying, etc.) within the channel configured to guide or direct the oneor more ion release member out of the cannulated body from the at leastone exit channel. The exit channels may be configured to allow tissue(e.g., bone) ingrowth, which may help with stability of the device onceimplanted. For example, the exit channels may be slightly oversizedcompared to the ion release members, permitting or encouragingin-growth. In some variations the exit channels may be doped orotherwise include a tissue-growth enhancing or encouraging factor (suchas a growth factor), or may be otherwise modified to encourage tissuegrowth.

In some variations the treatment cartridge may include a silver, zinc orsilver and zinc anode and the elongate body includes a cathode, whereinthe cathode has a higher redox potential than the anode. The cathode mayhave an irregular surface, or a high-surface area (e.g., per unitvolume); for example, the cathode may be formed of a foamed metal. Ingeneral the surface area of the cathode may be substantially greaterthan the surface are of the anode.

The treatment cartridge may be replaceable. For example, a treatmentcartridge may be configured to be removable from the cannulated body ofthe implant in situ, without removing the body of the implant from thedevice. Thus, the body of the implant may be structurally supportive(e.g., supporting the bone) while the silver-releasing portion may bere-charged by inserting another (replacement) cartridge after theprevious cartridge has corroded. For example, an elongate cannulatedbody may be configured as bone screw (e.g., an intramedullary bonescrew).

In some variations, an implant for providing antimicrobial treatment toa tissue includes: an elongate body having a threaded outer screwregion; an inner channel within the elongate body; a plurality of exitchannels extending from the inner channel and out through the threadedouter screw region; and a treatment cartridge configured to fit withinthe inner channel, the cartridge comprising a plurality of ion releasemembers configured to extend out of the exit channels.

As mentioned, the inner channel may include a guide element configuredto direct the release members out of the exit channels. The guideelement may be a shaped channel region (e.g., keying) or the like,configured to regulate the interaction between the implant body and thecartridge.

Any of the variations described herein may also include a tissuesampling feature. For example, the treatment cartridge may comprise asampler element configured to obtain a sample from a patient in whom abone implant has been implanted. A sampler element may be a regionconfigured to scrape, cut or otherwise remove a sample of tissue,particularly as the cartridge is removed from the implant. The sampledtissue may be examined for infection or the like.

Also described herein are systems for the controllable galvanic releaseof silver, zinc or silver and zinc ions from an implant to prevent ortreat infection. For example, a system may include: a threaded implantconfigured to be inserted into a bone and to hold an ion releasingtreatment cartridge; a cathode on the implant, the cathode comprising amaterial having a higher redox potential than the material of the anode(e.g., silver, zinc or silver and zinc); a treatment cartridgecomprising a silver, zinc or silver and zinc anode, wherein, when thetreatment cartridge is held by the implant, the cathode is in electricalcontact with the anode, driving the galvanic release of ions from therelease cartridge; and a switchable control configured to regulateelectrical contact between the anode and cathode.

In any of the variations described herein, the cathode may comprise amaterial selected from the group consisting of: palladium, platinum, andgold. The cathode and anode may be configured to generate a galvaniccurrent greater than about 0.2 μamps. The treatment cartridge mayinclude a plurality of ion release members configured to extend from theimplant when the cartridge is engaged therewith.

As mentioned above, any of the variations described herein may include aswitchable control configured to turn on and/or off the galvanicactivity between the anode and cathode. In some variations the switchmay be configured to electrically separate the anode and cathodepreventing or limiting the galvanic reaction. In some variations, theswitchable control may be configured for remote activation. For example,a switchable control may include a magnet.

Also described herein are methods of controllably delivering silver ionsfrom an implant to prevent or treat infection. Such a method may includethe steps of: engaging an implant with a removable ion-releasingtreatment cartridge, wherein the treatment cartridge comprises an anode(silver, zinc or silver and zinc), and wherein the implant includes acathode comprising a material having a higher galvanic potential thanthe anode, further wherein the cathode has a greater active surface areathan the active surface area of the anode; and activating a switchablecontrol to initiate the galvanic release of ions from the treatmentcartridge by placing the cathode in electrical contact with the anode.

The step of engaging the implant with the removably treatment cartridgemay include coupling the treatment cartridge with an implant alreadyinserted into a patient. The method may also include the step of placingat least a portion of the cathode in communication with a source ofoxygen at a concentration of greater than 7×10⁻⁵ mol/L. In somevariations, the implant may be implanted into a bone.

Also described are systems for the release of ions from an implant toprevent or treat infection, the system including: an implant configuredto hold a silver, zinc or silver and zinc release treatment cartridge; aremovable treatment cartridge comprising a silver, zinc or silver andzinc anode; and a cathode comprising a material having a higher redoxpotential than the anode, wherein the cathode is configured to bepositioned separately from the anode and in contact with an oxygen-richenvironment when the implant is implanted; wherein, when the treatmentcartridge is held by the implant, the cathode is in electrical contactwith the anode, driving the galvanic release of ions from the treatmentcartridge.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-1F illustrate the general concept of galvanic release of silverions.

FIGS. 2A and 2B illustrate one variation of an implant as describedherein.

FIG. 3 shows another variation of an implant as described herein.

FIG. 4 shows the implant of FIG. 3 in a deployed configuration.

FIG. 5 is another variation of an implant.

FIG. 6 is another variation of an implant.

FIGS. 7A-7C illustrate deployment of a silver eluting bone implant asdescribed herein.

FIGS. 8A and 8B illustrate deployment of another silver eluting boneimplant.

FIGS. 9A and 9B show a top view of an implant in a deployed anun-deployed configuration.

FIGS. 10A-10D illustrate variations of silver eluting bone implants asdescribed herein.

FIGS. 11A-11C illustrate another variation of an implant.

FIG. 12A shows another variation of a silver-eluting implant in adeployed and activated configuration (e.g., with silver release membersextended into the tissue) and FIG. 12B shows the same implant in ade-activated configuration, in which the silver release members havebeen withdrawn into the lumen/channel of the implant.

FIGS. 13A and 13B illustrate two variations of silver eluting boneimplants as described.

FIG. 14 illustrates another variation of an implant configured for useas a dental device. Similarly, FIGS. 15 and 16 illustrate variations ofsilver eluting bone implants configured to treat other bone regions,including the jaw and skull (face), respectively.

DETAILED DESCRIPTION

In some variations, the ion-releasing implants described herein areconfigured as bone screws for treating a bone in need of treatment, suchas a broken or osteoporotic bone. The ions released may be silver, zinc,or silver and zinc. Methods for treating a tissue (including bone) arealso described herein. For example, an implant may be configured as abone screw may align, biopsy, fuse, and/or stabilize a bone. The screwmay eliminate, prevent, or reduce an infection, such as a bacterial,protozoan, or fungal infection. The treatment from the screw may providesupport to the bone and may generate therapeutic silver ions toeliminate, prevent or reduce an infection.

In general, when two metals with different redox potentials are inelectrical contact and immersed in an electrolyte, one metal maypreferentially ionize and free electrons. As the free electrons migrateto the second metal, an electrical potential, called a galvanicpotential, is created. The process requires an electron acceptor, suchas oxygen near the second metal. When the first metal is silver, ionicsilver is released. Similarly, if the first metal is zinc, ionic zinc isreleased.

The devices and systems described herein are controllable ion-releasingsystems that are configured to allow the controllable release of ions(and particularly silver and/or zinc ions) into a body with sufficientconcentration and distribution to prevent or treat infection in thetissue while also providing structural support to the region andpreventing migration of the device. Various embodiments of these devicesare described and illustrated, however the general theory of operationof all of these devices may be similar. The devices or systems may beconfigured as bone implants that treat bone and surrounding tissue, byrelease of ions such as silver ions.

FIGS. 1A-F describe a simple galvanic cell setup such as for use in abody. The setup is shown treating an infection, but the same processcould be applied to healthy tissue to prevent an infection(prophylactically). The components including a first metal 2 (e.g.,silver), second metal 4 (e.g., platinum), and electrolytic fluid 6(e.g., blood) are shown individually in FIGS. 1A-1C and arranged in atissue in FIGS. 1D-1F. Electrolytic body fluid 6 is shown bathing orcontacting healthy tissue 10 as well as infected tissue 8. When silvermetal 2 contacts platinum metal 4 in body fluid 6, it forms a galvaniccell with a silver anode and platinum cathode. As shown in FIG. 1E,ionic silver 12 is generated and spreads through the body fluid, killingmicroorganisms and creating an infection-free zone 14 in body fluid 16in the vicinity of the anode. After treatment is complete, silver anode2 may be removed 20 leaving an infection-free body fluid 18.Alternatively, platinum cathode 4 may be removed; alternatively bothanode 2 and cathode 4 may be removed. Although the system is describedusing a silver metal anode and a platinum metal cathode, any metal witha higher redox potential than silver may be used as the cathode. Themetal may be a noble metal, such as gold, palladium or platinum. Forpurposes of illustration, the silver anode will be described as theremovable trigger for creating and stopping the galvanic response.However, either the silver or the metal with the higher redox potentialcan serve as a removable trigger (cartridge).

One embodiment of a device for controllably releasing silver is a bonestabilization device such, such as a bone screw. A bone stabilizationdevice may include a support region (e.g., an elongate rod, tube,channel, or the like) for insertion into the bone, and an insertionengagement region (e.g., a head, shoulder, coupling, etc.) for engagingwith an insertion and or removal tool. The insertion engagement regionmay be located at or near the proximal end, and may include an openingor engagement region for insertion and/or activation of a silver-release(e.g., galvanic silver release) cartridge. In some variations theengagement region includes a deployment mechanism (or contains andeployment mechanism) for activating and/or deploying silver-releasingmembers of a silver-releasing cartridge. The deployment mechanism may bereferred to as a deployment trigger. Examples of this are providedbelow.

For example, a stabilization device for controllable release of silvermay be configured as a silver-releasing bone screw. In general asilver-releasing bone screw is configured to controllably and/oractivatably release silver to prevent and/or treat infection. A bonescrew may include an elongate body (which may be threaded or otherwiseinclude one or more bone engagement surfaces) and an engagement regionat the proximal end configured as a head; one or more cartridges forgalvanic release may also be included to allow the device togalvanically release silver. For example, a bone screw according to thedisclosure may have a screw rod (elongate body) and one or morecartridges. The cartridge(s) may be configured to insert into the screwrod, and may be configured as an anti-infective cartridge or a biopsycartridge or both. A bone screw may have a platinum metal cathode and asilver metal anode. In some variations the cathode and/or the anode (orjust one or the other) may be present on the body of the bone screw; inother variations the cathode and/or anode (or both) may be present on acartridge that can be inserted and/or removed from the bone screw. Insome variations, the screw rod may be a platinum metal cathode and theanti-infective cartridge may be a silver metal anode. The cartridges mayalso include one or more anchoring, engagement, and/or stabilizationmembers that are configured to extend from the bone screw and into thebone. These members may be configured as arms, fingers, spikes, ribs,probes, struts, or the like, and may extend from the body of the bonescrew and into the tissue (including into the bone).

For example, in some variations, the screw rod is an elongated,cannulated (hollow), threaded rod. The rod may be externally threadedand/or internally threaded. Internal threads (or other guides/engagementregions) may be used to position and/or secure a cartridge within thebody. The screw rod may be sized and elongated to fit a specific type ofbone. The screw can fit any type of bone. By way of example, the screwcan be configured to fit a femur, metatarsal, tarsal, tibia, orvertebra. Threads on the outer surface of the screw rod may anchor thescrew rod into a bone or other body part. Thus, as mentioned, it may bethreaded or may include other externally-facing engagement regions. Thescrew rod may be cannulated along its entire length, or along part ofits length. The cannulated portion may create a fluid flow path. Fluid,such as oxygen carrying blood, may flow along the flow path and provideoxygen to create galvanic silver ion generation by the screw. In oneexample, the screw rod may be cannulated from a proximal end to part butnot all of the way to a distal end. The screw rod may be solid alongpart of its distal end. The solid distal end may be used to deflect aportion (e.g., anchoring, engagement, and/or stabilization members) of acartridge to be deflected from the cannulated inside to outside thescrew rod, and may also provide additional stability and/or strength tothe elongate body.

FIG. 2A shows one variation of a bone stabilization implant fordelivering an antibiotic (e.g., silver) in a controllable manner to aregion of bone and/or surrounding tissue. In this example the bonestabilization device is configured as a bone anchor screw including anelongated, cannulated screw rod 22 region. Screw rod 22 has elongatedbody 26 and threads 24. Threads 24 are configured to penetrate a part ofa bone and/or to hold the screw in place in a bone or body region.

The screw may have a screw head 28 at a proximal end with one or morefeatures to aid in holding, placing and/or removing the screw rod andfor inserting and/or activating the cartridge. FIG. 2A shows one exampleof a screw head configured as a grippable screw head 28. The screw headmay engage an insertion device and/or removal device. In some variationsthe screw may have a shaped head, such as hexagonal head 56 shown inFIGS. 5 and 6 that can be gripped by a wrench or other gripping tool.The feature may also be used to hold the rod screw in place whileinserting or removing a cartridge or performing other manipulations.

The inside of the screw rod may have connection means for connectingwith or attaching an insertion tool. In one example, the screw rod mayhave threads inside the screw rod (internal threads). The internalthreads may be along part or maybe along the entire internal length ofthe screw rod.

The bone screw example shown in FIG. 2A includes a screw rod with achannel or opening 30. The screw rod may have just one channel oropening or may have more than one channel or opening. The channels oropenings may be sized and shaped to allow at least part of a biopsycartridge and/or anti-infective cartridge to move outside cannulatedscrew rod.

The shape and pitch of the screw rod external threads may be angled orshaped to aid or direct cartridge placement. FIG. 2A shows screw rodexternal threads 24 that may aid placement of a cartridge. Thecannulated screw rod may have a port or ports (e.g., an opening) aroundthe channel that is configured to guide a portion of a biopsy elementand/or anti-migration/anti-infection element of a cartridge from insidethe cannulated screw rod to outside.

The screw rod may be made of any biocompatible material that issufficiently strong to be inserted into a body (bone) region. Forexample, the screw may be made, at least in part, of a steel (e.g.,stainless steel), or other material. In some variations, the screw rodis made of platinum, titanium, or stainless steel material that iscoated with platinum, palladium or gold. In particular, the screw rodmay be coated with a material or materials that are able to create agalvanic response with silver. The coating may be over the entiresurface of the screw rod or may be over part of the surface. The coatingmay be in the form of bands. The coating material may be a noble metalthat has a greater galvanic potential than silver in a body. The noblemetal may be gold, palladium, or platinum.

The rod screw may have features to increase its surface area. Inparticular, in variations in which the anode or, more likely, thecathode is located on the surface of the screw body, the portion of thescrew body forming the cathode may have a relatively large surface area(particularly as compared to the opposite redox partner, e.g., anode). Alarger surface area may create a higher galvanic current for generatingtherapeutic silver ions. The rod screw may comprise foamed metal on itsinside surface, outside surface, or both surfaces.

In some variations the screw or rod configured as a stabilization devicewith controllable silver release may include on ore more features toincrease opportunities for contact with body fluid. Increased contactmay allow a stronger, faster, or longer galvanic response. FIGS. 5 and 6show examples of rod screws 50, 51 with openings 60 along body 54 inaddition to openings near threads 51. These openings may allow increasedfluid flow, such as blood flow, around and through the rod screw. Someor all of these opening may also be configured to allow exit of one ormore members (e.g., arms, struts, etc.) from a cartridge.

Any of the devices described herein may include or be configured for usewith one or more cartridges. In general, a cartridge is aremovable/replaceable element that may be inserted into or alongside ofthese support and antimicrobial devices (e.g., screws). As mentionedabove, the cartridge may include one or more members that are configuredto be extended out of the device and into the surrounding tissue. Thesemembers may be referred to and configured as struts, probes, legs, arms,hooks, wires, coils, fingers, spikes, ribs, or the like; in general theyare elongate members that may be inserted into the patient's tissue andextend away from the body of the device. The members may therefore beconfigured to help secure the device within the tissue. For example, themembers may enhance the mechanical attributes of the device, includingpreventing the device from pulling out of the tissue.

A cartridge may be referred to as an anti-infection cartridge if it isconfigured to aid in the release of silver ions from the device. Forexample the cartridge may include one or more members having silver(e.g., anode) regions or configured so that an entire member is silverreleasing. In some variations the cartridge may also be referred to as abiopsy cartridge that is configured to remove tissue (e.g., bone, softtissue, etc.) for testing. In some variations the cartridge may beconfigured as both an anti-infection and a biopsy cartridge.

An anti-infection cartridge may include a cathode. For example, thecartridge may include a plurality of arms, some of which are formed of ametal such as platinum that can react with the silver anode to releasesilver. As mentioned, in some variations the body of the implant devicemay include all or portion of the cathode.

In the examples illustrated herein the treatment cartridges are shown asseparate elements that may be inserted into the devices. For example, acartridge may be inserted into the device after the device (e.g., screwbody) has been implanted into the bone. Cartridges may be replaced orrecharged (e.g., replacing a portion of a cartridge such as asilver-containing member) without removing the entire device from thepatient.

In some variations the cartridge is integral with (or part of) theimplant device (e.g., screw).

The anti-infection cartridge may serve other functions in addition to orinstead of being anti-infective. For example, it may be configured toprevent device migration. In some variations, including thoseillustrated below, a plurality of member extend from the device body(e.g., the body of the bone screw) and push into the tissue to helpanchor the device. Thus, the cartridge member(s) may be configured topenetrate tissue, including bone. In some variations the members arerigid/stiff member and may also include tissue-penetrating distalregions. For example, one or more members may be stainless steel, nickeltitanium, or the like (which may be coated with silver in somevariations).

Thus, an anti-infection cartridge may comprise silver or a silvercoating, plating, or the like. The anti-infective cartridge may beconfigured to be easily inserted and/or easily removed from thecannulated device (e.g., screw). In some variations, the cartridge has aholding end and a probe end. The holding end may be configured to bereadily held, gripped or grabbed by a hand or by a device. By way ofexample, the holding end may be a loop, V shape or U shape, or mayinclude a grip region. The probe end may be configured to contact a bodypart or a body solution. In general, the probe end is configured as oneor more members that extend from the implant device when it isimplanted. For example, the probe end may be configured as one or moremembers that extend from the screw rod. This may allow the silver ionsto be directed to a particular body region, or it may create a largerregion of therapeutic silver ions, or it may allow the cartridge tobetter contact or grip or hold a body surface.

FIG. 2B shows one example of an anti-infection cartridge 32; theproximal end may be referred to as the holding end 37, which can begripped by a hand or tool. The distal end of the cartridge in thisexample has two probe ends that can extend out of the body of the screwdevice. In FIG. 2B, the ends 33, 35 of the two members of the cartridge32 can be inserted into a screw rod portion of a screw of rod forimplantation into the body (bone). In this example the body of the screwrod includes a cathode 22 along the outer surface of the screw; theanodes on the elongate members of the cartridge contact the cathodalsurface of the screw when they are extended from the implant. Each probeof the cartridge may have multiple probe ends. The probe ends may beconfigured to contact a portion of the bone or other tissue to hold thecartridge and bone screw in place. The probe ends may be positioned(spread apart) to create a larger area of effective silver ion area.

The anti-infective cartridge may be placed in contact with a screw rodto generate a galvanic screw in variations having the anode(s) on thecartridge and the cathode on the body of the implant (e.g., screw). Forexample, FIGS. 3 and 4 illustrate placement of an anti-infectivecartridge 32 such as the one shown in 2B in contact with a screw bodysuch as the one shown in FIG. 2A. The cartridge arms are extended inFIG. 4. In this example the cartridge includes two members, each formedof the twisted wires shown. In one variation the wires are both silverwires; alternatively one wire may be silver and the other wise stainlesssteel or the like, adding column strength for insertion, such as may behelpful for use in bone. For example, in FIG. 3 the probe ends of thecartridge pass through the center of cannulated screw rod 26 and may beheld there until they are deployed into the tissue. When they aredeployed (e.g., after implanting the device into the bone) the implantmay include deflection/guide regions that steer the members out of theimplant and into the tissue. For example, the threads 24 of the screwbody in FIGS. 3 and 4 may receive or guide the probe ends as they exit.As the cartridge 32 is advanced, probe ends 33 and 35 exit throughopenings 30 in the screw body. As mentioned, extending the probes intothe tissue may provide mechanical resistance to inhibit unwanted removalor movement of the probe and/or screw. In some variations the distal endof the probes may be sharp or otherwise tissue penetrating.

A biopsy cartridge may share many similarities with an antimicrobialcartridge as described above. For example, the biopsy cartridge mayinclude one or a plurality of members configured to extend from the bodyof the implant device (e.g., arms, struts, etc.). In some variations thedistal ends of these members may include one or more tissue captureelements such as a cup, hook, scraper, basket, needle, etc. A cartridge(including a biopsy cartridge) may also include an attachment site orcoupling for a proximal handle (e.g., a threaded region or the like). Insome variations a biopsy cartridge may be paired with an antimicrobialcartridge and the two may be exchanged from the same implant device. Forexample, the implant device (e.g., screw body) may be inserted and anantimicrobial cartridge and a biopsy cartridge may be alternatelyinserted to sample, then treat, then sample (in any appropriate order)the bone. In some variations the members of the biopsy device are longer(or are capable of extending to a longer length) than the members of theantimicrobial cartridge, to sample bone regions beyond the sites inwhich the members of the antimicrobial cartridge resided. In somevariations the insertion length of the cartridge member(s) is variable,and may be selected or modified by a user when inserting or deployingthe cartridge.

FIGS. 7A-C, 8A, 8B, 9A, and 9B describe another embodiment of a galvanicscrew system for treating or preventing infection. These systemstypically include a support device body (e.g., screw or rod body) andone or more cartridges, as described above. A screw system may have acollapsed or un-deployed configuration and an expanded or deployedconfiguration. In some variations, toggling between the deployed andun-deployed configurations controls the galvanic potential. For example,in some variations, extending the members of the cartridge including thesilver anode may start the galvanic current by placing the anode inelectrical contact with the cathode.

Additionally, because of the relatively streamlined initial size/shape,the un-deployed configuration of the system/device can readily beinserted into a bone in a less invasive way and expanded into thedeployed configuration once it is place, limiting any damage or traumato the tissue.

When the screw is in an un-deployed configuration, the galvanicpotential is essentially off. When the screw is in an expanded position,the cathode and anode are in electrical contact with each other and thegalvanic potential is on. As the amount of silver in the implant may belimiting, it may be useful to keep a galvanic potential turned off whenit is not needed and conserve the potential for future use. The implantmay be kept in the collapsed (off) or partially collapsed (off)configuration for any reason. For example, the implant may be configuredto be switched “off” (stopping the galvanic release of silver) if thereis no evidence of a current infection, but a future infection may beexpected, as might be the case in a joint implant. Joint implants havebeen reported to develop infections months or years after beingimplanted. By implanting one of the devices as described herein forcontrollably delivering silver, but leaving galvanic potential “off”,the implant may conserve the silver for use if and when an infectiondevelops.

Thus the devices and systems described herein may be configured to allowthe anode to be electrically isolated from the cathode (switching “off”the delivery of silver by the device) until it is desired to becontrollably released. For example, the electrical connection betweenthe anode and the cathode may depend upon the extent to which acartridge having members is extended from the body of the device. Insome variations, a conductive bridge (e.g., switch) between the anodeand cathode may be moveable into and out of position to turn “on” or“off” the galvanic reaction. This is described below in reference toFIGS. 12A-12B. In other variations a switch is not necessary, as theanode and cathode may be place in electrical connection by fully orpartially deploying the cartridge (e.g., the members of the cartridge);in the un-deployed configuration the anode may be electrically isolatedfrom the cathode.

In some variations, the activation of the silver release from theimplant may depend upon controlling exposure of the anode and/or cathode(which may be in electrical contact) to an electrolytic solution. Forexample, the cathode and/or anode may be retracted into thefluid-impermeable body of the device until it is desired to releasesilver ions.

Note that the controllable release of silver as described herein mayalso refer to the controllable distribution of silver released into thebody. In some variations the pattern of distribution of the silver inthe body may be determined in part by the arrangement of the member inthe deployed configuration. As the members are expanded away from thebody of the device (e.g., the screw body or rod body) a much largerpattern (e.g., “cloud”) of silver ions having antimicrobial effects at alarger concentration could be achieved than in comparison to an implantor device having only a coating of silver, even actively releasedsilver. In some variations, the implant may be configured to allowcontrol of the extent of the deployment of the members; for example,extending the device only partially from the body of the device asillustrated in FIGS. 7A-8B.

FIGS. 7A-7C show a device for controllably delivering silver ions thatis configured as a screw 60; in this example, the screw has beeninserted in a bone 62 having a infected region 66. The implant is bathedin a body fluid 64. FIGS. 7B-7C show views along line 2B of FIG. 7A,showing the internal cannulated passage through the elongate screw body76. The implant is anchored in cancellous bone 82 initially by threadedportion 78, with the rest of implant body 76 in this example positionedwithin the cortical bone 80. In this example, six members formed asanodes (silver containing regions) are configured as ribbon coils 84that can be rotated to deploy them out of openings 74 on the body of thescrew. The ribbon coil 84 is held inside rod screw 60 nearslots/openings 74 between threads 78. These deployable members are partof the loaded (e.g., preloaded) antimicrobial cartridge 72. Thecartridge may be rotated when positioned within the screw body to deploythe members from the screw and into the tissue. The device also includesa screw head 68 at the proximal end and a deployment trigger 72 which isconfigured as a trigger head 72 in this example. Screw head 68 has slots70 which can be used to insert (e.g., screw in) the screw into the bone,and/or to hold screw body when manipulating trigger head 72 or can beused to otherwise insert, remove, or manipulated the screw.

In the exemplary device shown in FIGS. 7A-7C, the silver releasingmembers of the cartridge may be deployed by rotating the trigger.Referring to FIG. 7C, the trigger head 72 may be rotated (e.g.counterclockwise), causing ribbon coils 84 to move into position underslots 84 and to unfurl to form probes 88 that extend from the elongatebody of the screw. As the members extend from the body, silver on themembers (forming a cathode) is placed in electrical contact with thecathode formed on the outer surface of the screw body 76; thus thegalvanic potential is on, and silver may be released into the tissuethat is bathed in the electrolyte solution (e.g., blood). Thus, members88 include a silver-releasing anode that is electrically communicatingwith the platinum cathode on the screw body 76. In this manner, silverions may be released in a region surrounding the implanted screw body,and silver ions 90 may clear infection 66 to create a clear zone 88 intissue around the implant.

In the example shown in FIGS. 7A-7C the device for antimicrobial silverrelease may include a cartridge having the coiled arms that can beextended from the body. In some variations, the cartridge is integralwith the body of the device. For example, in FIGS. 7A-7C the cartridgecomprises the inner rod member connected proximally to the trigger; thecartridge includes the coiled member wrapped around the inner rodmember. The inner rod member may be rotated within the body. In somevariation the inner rod member is permanently fixed within the body ofthe device. In some variations the inner member forming the rotatablemay be removable from the body of the device. Thus, the inner member maybe recharged and/or replaced while leaving the screw within thepatient's bone.

FIGS. 8A and 8B show another variation of a device configured as a screwsimilar to the one in FIG. 7A-C with tilted slots 104 between threads102 on rod region 100 in order to bias ribbon coil 106 to exit the bodyat an angle. In general, the device body may include one or more guides,channels, or the like for directing the members (“ribbon coil 106”) fromthe cartridge (e.g., inner rod) away from the body of the device at anangle or along a pathway. For example, in some variations the device'sthreads near the distal end of the device may be used to deflect anddirect the extending members and thereby control the extent and locationof antimicrobial “cloud” surrounding the implant as the ions arereleased.

FIGS. 9A and 9B show a top view of another variation of a deviceconfigured as a screw similar to the ones shown in FIGS. 7A-8B. Thisvariation includes more members (probes 114), which may be distributedmore tightly or specifically around the device. In this example, thetrigger head 108 is shown inside rod screw head 110. Slots 112 on screwhead 110 can be used to hold the device head 110 relative to triggerhead 108 to manipulate the trigger relative to the screw, or screwrelative to the bone. In another example, the interior surface and/orouter surface of the screw head 110 may be shaped to engage and/or begrippable by a cannula or other insertion/removal device during screwinsertion, removal, or repositioning. The internal shape of the proximalend of the device may be any shape that allows an insertion/removaldevice to grip the internal surface and to move (e.g. rotate) the screw.The internal shape may be, for example, hexagonal, square, triangular,or threaded. The internal shaping may be only in the head or may extendthrough part or the entire length of the screw. Being able to grip morethan just the head of the screw may better distribute force applied(e.g. torque) to move the screw (e.g., during insertion, removal orrepositioning) and thereby prevent the screw from breaking, stripping,or otherwise being damaged. When the multiple arms (probes, coils, etc.)are extended into the tissue (e.g., bone) from within the bone implantdevice, these member may (in addition to releasing silver) providedadditional anchoring to the implanted device. For example, theextended/deployed arms provide mechanical resistance to inhibit unwantedremoval or movement of the device.

In general, the cartridges described herein can be assembled from anymaterials that will allow them to be deployed from an implanted deviceand release silver ions and/or remove (biopsy) tissue. For example,FIGS. 10A-10D show a device, configured as a screw, and a cartridge,formed from a memory shaped ribbon. FIG. 10A shows the shape of theribbon 124 and the screw device 120. In this example, ribbon 124collapses to assume collapsed configuration 126 as it's inserted intohousing 120. Collapsed ribbon 126 is pushed or turned into position sothat probes 125 can expand through slots 122.

Bones that have been subject to mechanical trauma, infection or otherforms of insult may be prone to further damage during insertion of abone screw. Inserting a bone screw with mechanical properties that arecloser to those of bone may reduce or prevent further trauma. FIGS.11A-C show a bone screw in which the mechanical properties of the bonescrew are relatively similar to the mechanical properties of the bone,but which is still able to generate therapeutic silver ions. In thisexample the elongate body of the device 130 includes a threaded distalend region and a proximal spring region. The device is shown in FIG. 11Band the cartridge for use with the device is shown in FIG. 11A. FIG. 11Bshows a platinum (or platinum coated) screw with a threaded distal end134 and a proximal spring end 137. Screw end 134 may be inserted into abone by turning hex 136 with a driver. In any of the variationsdescribed herein, an initial (e.g. pilot) passage into the bone may bedrilled or otherwise formed before implanting the device. Stop 138 maybe used to prevent the screw from being inserted too far into the bone.Once rod screw 130 is in place, a cartridge comprising, in this example,a silver screw or spring 132 as shown in FIG. 11A can be screwed intorod screw 130. The result is the two springs coiled together 144 asshown in FIG. 11C. The contact between the platinum or platinum coatedcoiled region of the device body 137 and the coiled and silver or silvercoated region of the cartridge 132 is sufficient that when in thepresence of an electrolytic solution, silver ions will be released fromthe implant.

Another example of a trigger or switch for controlling the release ofsilver ions (e.g. for creating a device having a controllable on/offapplication of silver ions) uses a magnet as shown in FIGS. 12A-12B. Inthis example a control magnet is shown outside the body, external toskin 155 while screw 152 is shown screwed into cortical 154 andcancellous 156 regions of bone 152 in the body. Application of externalmagnetic force (e.g., magnet 158) repels or attracts a correspondingmagnetic region within the implant 160, causing it to move the cartridge162 into or out of position to expand probes 162 out of screw 150 orretract them into the screw. For example, in FIG. 12B, application ofexternal magnet 158 attracts the internal cartridge implanted with thescrew, causing it to move the cartridge 164 towards it in a contractedposition. Lateral movement of the cartridge results in extending orretracting the members of the cartridge into and out of the screw body,thereby turning on or off the release of silver ions from the screw.

In use, several bone screws can be used together for larger bones orbones otherwise requiring more support or treatment as shown in FIGS.13A-13B. For example, FIG. 13A shows a series of bone screws 190inserted through a bone plate 190 that is adjacent to a cortical bone194 and treating large infection 188 near fracture 186 in femur 180.Each screw has multiple silver-releasing members 194 extending intocancellous bone 184 to create a large silver therapeutic area. FIG. 13Bshows an alternative embodiment in which some silver/silver coated rodscrews 196 are alternating with platinum plated or noble metal rodscrews 198.

The bone screw, methods, and systems described herein may be used withany type of bone, including long bones. FIG. 14 shows a bone screw 202configured to release silver ions similar to those in FIGS. 2A-3B above,inserted into a portion of a jaw. Therapeutic silver ions 206 arereleased from members 206. The screw may be configured to attach atooth, crown or other dental appliance. FIG. 15 shows bone screws and aplate attached to a mandible such as might be used in a reconstructivesurgery to prevent or treat infections. FIG. 16 shows bone screws andplates used in various bones of the jaw, face, and skull 220.

In some variations, the anti-infective cartridge includes a lock on thecannulated screw and/or rod to hold the cartridge in place relative tothe elongate body of the device. Thus, the cartridge may be locked in aconfiguration (e.g., deployed, un-deployed, etc.) within the body of thedevice. The lock may be releasable; for example, the lock may include alatch.

As mentioned above, the cartridge may be configured as a biopsy (e.g.,assay) cartridge, which may be used instead of, or in addition to ananti-infection cartridge; in some variations the cartridge is acombination of both anti-infective and biopsy. In general a biopsycartridge may be coupled to the body of the device and used to withdrawa sample of tissue from around where the implant has been insertedwithout having to remove the device (“implant”) from the body. Forexample, in some variations, the biopsy cartridge is inserted throughthe cannulated elongate body of the device (e.g., of a screw body) andone or more members of the cartridge extends from the elongate body,similar to the silver-releasing members extending from thesilver-release cartridges described above, to make contact with aportion of the body to be assayed, to obtain a biopsy (assay) sample,and to be removed. The biopsy sample can be assayed in any way afterbeing removed from the patient. Thus, the biopsy cartridge may have anexpanded (deployed) form and a collapsed (un-deployed) form. The biopsycartridge may be expanded before obtaining a biopsy sample and may becollapsed after obtaining a biopsy sample. Any of the structuresdescribed in the disclosure for the anti-infective cartridge and any ofthe methods described for inserting, using, or removing the cartridgemay also or instead be used for the biopsy cartridge.

Although many of the examples described above are configured so that thedevice body is configured as the cathode (e.g., comprising a platinummaterial) while the extendable members from the cartridge are the anodematerial (e.g., silver or silver coated), in some variations thisconfiguration may be reversed. For example, the device body (e.g., thescrew body, rod body, etc.) may be silver or silver coated and theanti-infective cartridge may configured as the cathode, comprising anoble metal such as gold, palladium or platinum to create a galvanicresponse in the body and release silver ions.

In general, the devices may be inserted or implanted into the body,e.g., into the bone, either before during or after engaging a cartridge,including an anti-infective and/or biopsy cartridge. For example, adevice configured as a silver-delivering screw may be inserted into abone, loaded with an anti-infective cartridge or biopsy cartridge byinserting the cartridge through the elongate body (e.g., from theproximal end of the screw rod). A biopsy cartridge may be inserted andremoved before, after, or instead of insertion of an anti-infectivecartridge. In one example, a biopsy cartridge is inserted through thedevice body, takes a biopsy sample, and is removed before anti-infectivecartridge is inserted. In another example, an anti-infective cartridgemay be inserted, left in the body for a period of time to createtherapeutic silver ions, and removed before a biopsy cartridge is usedto remove a biopsy sample to determine an effectiveness ofanti-infective treatment. In another example, an anti-infectivecartridge may be inserted, left in the body for a period of time tocreate therapeutic silver ions, and removed before a biopsy cartridge isused to remove a biopsy sample to determine an effectiveness ofanti-infective treatment.

In another example, a first anti-infective cartridge is placed throughthe device implanted in the body and one or more anti-infectivecartridges are additionally placed in the device body, without removingthe first anti-infective cartridge. The cartridges may degrade (e.g.,corrode as the silver is release) or simply avoiding by precedingcartridges.

In another example, a first anti-infective cartridge may be removed froman implanted device in a body and a second anti-infective cartridgeinserted. This process may be repeated. This may be done, for example,if there is insufficient therapeutic silver remaining on a firstcartridge. The screw rod and any of the cartridges may be left in thebody for any length of time. They may be left in for less than thirtydays (e.g. a few days, a week, or several weeks) or they may be left infor more than thirty days. In one example, the screws may be left inpermanently.

Examples

Any of the exemplary ion-releasing devices described above may be usedto treat (or prophylactically treat or prevent) infection and/or supporttissue. Exemplary methods of use are illustrated below. These examplesare intended only to illustrate how one such implant may be operated,and is not intended to be limiting or limited to any specific variation.

In general, the implants for controllably providing antimicrobialtreatment and support may be used to treat any tissues of the body, butparticularly bones, including the long bones (such as the femur, tibia,radius, ulna, fibula, metacarpal, metatarsal, phalanges, etc.), thespine, and the skull. In some variations the device is configured forinsertion into the medullary canal of a lower extremity bone, such as afemur, tibia, tarsal or metatarsal, for the alignment, stabilization,fixation and bone biopsy of various types of fractures or deformitiescaused by trauma, infection or disease. Examples of such fracturesinclude: traumatic fractures, re-fractures, non-union, reconstruction,malunion, malalignment, pathological fractures due to infection ordisease and impending pathological fractures. The ion controlled releasesystems may have silver and/or zinc coated struts that expand out fromthe body of the device to form a three-dimensional array to stabilize,minimize device migration and form an antimicrobial barrier to reducemicrobial colonization on the external surfaces of the device.

An implant that controllably provides antimicrobial treatment, such as abone screw for controllably releasing silver ions, may be used to repaira bone fracture. The bone may first be prepared to receive the device.Pre-existing deformities may be corrected prior to the preparation andinsertion of a device such as those described above configured as acontrollable silver-ion releasing bone screw (e.g., intramedullary or IMscrew). The anatomy of the deformity, surgeon preference, and patientpositioning may determine the appropriate approach chosen for jointpreparation and alignment.

For example, a bone implant that controllably provides antimicrobialtreatment may be use used to repair a broken ankle. Upon properlyaligning and preparing all the joint surfaces, the ankle may bepositioned for arthrodesis. The ankle may be medizlized by thoroughdebridement of medial gutter facilitates positioning in the center ofthe calcaneus, talus and tibia. The ankle may then be placed in neutraldorsiflexion and symmetric external rotation of the contralateral ankle.This position may be maintained throughout the procedure, and may befacilitated by provisionally placing a wire on the periphery of theankle joint.

Under fluoroscopic control, a 2-3 cm longitudinal incision may be madejust above the location for the bone insertion point. After the incisionis made, dissection may be continued down to the surface of the targetbone by bluntly dissecting through the soft tissues, noting the locationof neurovascular bundles. Thereafter, the device (e.g., a controlledsilver ion releasing implant or bone screw) may be inserted. Anintroducing cannula can then be selected and placed against the boneinsertion point. The hand reamer may then be used to carefully reamthrough the cortical bone into the intramedullary canal. The cannula isnot advanced into the bone. The position of the hand reamer underfluoroscopy may be monitored under fluoro periodically. The hand reamercan be removed from the cannula.

Thereafter, the surgeon may select the proper size implant device IMscrew rod that is pre-mounted on trocar. Advance the screw rod into thebone by turning clockwise. Periodically stop and check under fluoroscopythe position of the screw rod with respect to the opposite corticalside.

Finally, the trocar device may be removed from the inside of thecannulated screw rod by turning clockwise.

In some variations, the bone implant that controllably providesantimicrobial treatment may also be used to take a biopsy before, duringor after insertion of the implant. The implant may be inserted into thebone as discussed above, and a bone biopsy cartridge may be insertedthrough the internal cannula of the implanted device. The proximal endof the cartridge may be grasped direction of coupled to a handle formanipulation by a surgeon. The distal end of the biopsy cartridge mayinclude one or a plurality of cupped wires that can be extended from theimplant body and used to sample the tissue. For example, one or morecupped wires may be deployed through the ports of the body of ascrew-type implant. This may be met with some resistance from thecancellous bone. Extension of the biopsy cup wires can be confirmed byfluoroscopy. After deployment of the wires, the proximal end of thecartridge may be pulled back and the wires retracted, capturingcancellous bone for biopsy in the cups of the cartridge. The cartridgemay be removed from the rest of the implant, and placed in a sealed,labeled laboratory infectious disease container for further processing.

In general, the antimicrobial cartridges described herein may beinserted and/or deployed as mentioned above. For example, a cartridgemay be removed from a foil sterile package. The cartridge may be storedin a sealed package with an indicator to indicate if the packageintegrity has been compromised. For example, the package may include anindicating desiccant (e.g., pouch) that visually indicated, e.g., by aline that changes red, if the packaging has been breached and exposed tohumidity.

The cartridge may be inserted into the device housing, e.g., the centralbore or cannula within the elongate cannulated body. In some variationsthe cartridge is pre-loaded into the body of the device. The cartridge,and particularly the elongate members of the cartridge at the distalend, may be inspected and/or aligned with the cannulated body so thatthey may be extended through openings in the body to extend from thebody when implanted. The cannulated body may include a guide, channel,keying, etc. to aid in aligning and inserting the cartridge into thebody. In some variations the inner surface of the cannulated body iskeyed (including threaded) to guide the insertion of the cartridge; anouter surface of the cartridge may mate with and engage the innersurface of the cannulated body.

An insertion tool (e.g., handle) may be used to help insert thecartridge into the elongate cannulated body of the implant. For example,the insertion/removal tool may be an elongate rod having a coupling andor mount its distal end region to connect to a cartridge. In somevariations the insertion/removal tool may include an inner body regionfor holding the cartridge in the collapsed/un-deployed configurationafter or before it has been connected/removed from the implant body. Forexample, the cartridge may be “collapsed” by the action of the insertiontool. The distal end of the insertion tool may include a chamber,cannula, etc. for holding the cartridge in a collapsed configuration;the cartridge may be pushed out of or otherwise extended from the handleinto the implant, allowing the members of the cartridge to extendthrough the body of the device and into the tissue.

Thus, the distal ends of the members may be extended away from the bodyof the implant and into the patient tissue so that the members willdeploy through the ports of the device. In some variations thisdeployment is guided by the implant body which deflects and/or guidesthe members as they are extended. For example, the threads of an implantconfigured as a bone screw may be arranged to deflect the membersoutward and into the tissue. After insertion and/or deployment of thecartridge in variations requiring it, any inserter tools may bewithdrawn and proper positioning may be confirmed using fluoroscopy.

Thereafter, the stability and operation of the device may be verified,and the surgical access/insertion site may be closed, at least for someamount of time. In some variations the cartridge may bereplaced/recharged into the same implant over the course of weeks,months or years.

Once the implant has exceeded its useful life, it may be removed fromthe patient or left in place. In some variations it may be desirable toleave the implant in place so that it can continue to provide structuralsupport. This may be true even of the cartridges, as any extendedmembers that have been extended into the tissue may continue to providestructural support even if the source of silver ions has been exhausted.

The cartridges may be removed in many cases by reversing the insertionprocess just described. In some variations the cartridge may remainwithin the bone for approximately 30 days or more. The implant may beremoved with a removal device configured to couple to the proximal endof the cartridge and/or to release the cartridge from the device body.

In some variations a retrieval kit may be used. For example, a retrievalkit may include a removal device (configured similarly to an inserter).To remove the device, surgical aseptic technique (under fluoroscopy) maybe used to make a small incision directly above the site of the previoussurgery. The removal device (cartridge retrieval device) may be insertedand attached to the proximal end to the outer housing to stabilize it.In some variations the retrieval device has an elongated body with adistal end that is adapted to couple or abut the implant device body anda second region that is configured to couple with the proximal end ofthe cartridge. For example, the retrieval member may include a centralshaft having a distal end adapted to couple (e.g., screw onto) theproximal end of the cartridge and an outer cannula surrounding thecentral shaft that is configured to couple to the proximal end of theimplant device. In some variations the retrieval device includes aproximal forceps that may be used to couple to the inner cartridge. Suchconfigurations (or similar configurations) may allow sufficient leverageto remove the extended members and withdraw the cartridge form theimplant and the body, retracting the members through the outer housingports and collapsing them for removal.

After removal, the cartridge may be disposed of or used to providebiopsy material. The surgical site may be examined directly and byfluoroscopy. If it appears that the site (and implant) would benefitfrom additional anti-migration or anti-infection elements, a newcartridge may be re-deployed for another treatment period (e.g., 30days) and the process repeated.

Although the illustrations described above illustrated primarilythreaded screw variations, it should be apparent that non-treadedvariations and non-screw variations are contemplated. For example, thedevices for controllable release of silver ions described herein may beconfigured as nails, rods or the like.

As for additional details pertinent to the present invention, materialsand manufacturing techniques may be employed as within the level ofthose with skill in the relevant art. The same may hold true withrespect to method-based aspects of the invention in terms of additionalacts commonly or logically employed. Also, it is contemplated that anyoptional feature of the inventive variations described may be set forthand claimed independently, or in combination with any one or more of thefeatures described herein. Likewise, reference to a singular item,includes the possibility that there are plural of the same itemspresent. More specifically, as used herein and in the appended claims,the singular forms “a,” “and,” “said,” and “the” include pluralreferents unless the context clearly dictates otherwise. It is furthernoted that the claims may be drafted to exclude any optional element. Assuch, this statement is intended to serve as antecedent basis for use ofsuch exclusive terminology as “solely,” “only” and the like inconnection with the recitation of claim elements, or use of a “negative”limitation. Unless defined otherwise herein, all technical andscientific terms used herein have the same meaning as commonlyunderstood by one of ordinary skill in the art to which this inventionbelongs. The breadth of the present invention is not to be limited bythe subject specification, but rather only by the plain meaning of theclaim terms employed.

What may be claimed is:
 1. A method of controllably delivering silver,zinc, or silver and zinc ions from an implant to prevent or treatinfection, the method comprising: engaging the implant with a removablesilver, zinc or silver and zinc releasing treatment cartridge, whereinthe treatment cartridge comprises a silver, zinc, or silver and zincanode, and wherein the implant includes a cathode comprising a materialhaving a higher half-cell potential than the anode, further wherein thecathode has a greater active surface area than the active surface areaof the anode; and activating a switchable control to initiate thegalvanic release of silver, zinc or silver and zinc from the treatmentcartridge by placing the cathode in electrical contact with the anode.2. The method of claim 1, wherein engaging the implant comprisescoupling the removable silver, zinc or silver and zinc releasingtreatment cartridge with the implant when the implant is alreadyinserted into a patient.
 3. The method of claim 1, further comprisingplacing at least a portion of the cathode in communication with a sourceof oxygen at a concentration of greater than 7×10⁻⁵ mol/L.
 4. The methodof claim 1, further comprising inserting the implant into a patient'sbody.
 5. The method of claim 1, further comprising inserting the implantinto a bone.
 6. The method of claim 1, further comprising screwing theimplant into a subject's bone.
 7. The method of claim 1, whereinactivating comprises inserting the removable silver, zinc or silver andzinc releasing treatment cartridge into the implant so that the cathodeis in electrical contact with the anode.
 8. The method of claim 1,wherein engaging comprises mating the removable silver, zinc or silverand zinc releasing treatment cartridge with a channel in the implanthaving an opening so that the removable silver, zinc or silver and zincreleasing treatment cartridge extends through the opening in theimplant.
 9. The method of claim 1, wherein engaging the implantcomprises engaging a bone-screw implant having a threaded out screwregion with the removable silver, zinc or silver and zinc releasingtreatment cartridge.
 10. The method of claim 1, wherein engaging theimplant comprises extending a plurality of silver, zinc, or silver andzinc release members forming the removable silver, zinc or silver andzinc releasing treatment cartridge from openings in the implant body.11. A method of controllably delivering silver, zinc, or silver and zincions from an implant, to prevent or treat infection, the methodcomprising: engaging the implant with a removable silver, zinc or silverand zinc releasing treatment cartridge, wherein the treatment cartridgecomprises a silver, zinc, or silver and zinc anode, and wherein theimplant includes a cathode comprising a material having a higherhalf-cell potential than the anode; and initiating the galvanic releaseof silver, zinc or silver and zinc from the treatment cartridge byplacing the cathode in electrical contact with the anode, wherein theimplant comprises a threaded outer screw region.
 12. The method of claim11, wherein engaging the implant with the removable treatment cartridgecomprises coupling the treatment cartridge with the implant when theimplant is already inserted into a patient.
 13. The method of claim 11,wherein engaging the implant with the removable treatment cartridgecomprises coupling the treatment cartridge with the implant before theimplant is inserted into a patient.
 14. The method of claim 11, furthercomprising placing at least a portion of the cathode in communicationwith a source of oxygen at a concentration of greater than 7×10⁻⁵ mol/L.15. The method of claim 11, further comprising inserting the implantinto a patient's body.
 16. The method of claim 11, further comprisinginserting the implant into a bone.
 17. The method of claim 11, whereinactivating comprises inserting the removable silver, zinc or silver andzinc releasing treatment cartridge into the implant so that the cathodeis in electrical contact with the anode.
 18. The method of claim 11,wherein engaging comprises mating the removable silver, zinc or silverand zinc releasing treatment cartridge with a channel in the implant sothat the removable silver, zinc or silver and zinc releasing treatmentcartridge extends through an opening in the implant.
 19. The method ofclaim 11, wherein initiating the galvanic release comprises activating aswitchable control.
 20. A method of controllably delivering silver,zinc, or silver and zinc ions from an implant, to prevent or treatinfection, the method comprising: engaging the implant with a removablesilver, zinc or silver and zinc releasing treatment cartridge, whereinthe treatment cartridge comprises a silver, zinc, or silver and zincanode, and wherein the implant includes a cathode comprising a materialhaving a higher half-cell potential than the anode; extending aplurality of silver, zinc, or silver and zinc release members formingthe removable silver, zinc or silver and zinc releasing treatmentcartridge from openings in the implant body; and initiating the galvanicrelease of silver, zinc or silver and zinc from the treatment cartridgeby placing the cathode in electrical contact with the anode, wherein theimplant comprises a threaded outer screw region configured for insertioninto a bone.